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Toxicological information

Developmental toxicity / teratogenicity

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Administrative data

Endpoint:
developmental toxicity
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Report Date:
1992

Materials and methods

Principles of method if other than guideline:
according to OECD Guideline 422 (Combined Repeated Dose Toxicity Study with the Reproduction / Developmental Toxicity Screening Test)
GLP compliance:
yes
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
rat
Strain:
other: Crl: CD BR
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River LAboratories, Kingston, NEw YOrk, USA
- Age at study initiation: (P) 10 wks;
- Weight at study initiation: (P) Males: 204.6 -230.7 g; Females: 166.5 - 195.9 g;
- Fasting period before study: no
- Housing: individually during pretest, premating, gestation; as breeding pais and as litters during lactation
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): adlibitum
- Acclimation period: 5 weeks

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
other: 0.5% aqueous methyl cellulose
Analytical verification of doses or concentrations:
yes
Details on analytical verification of doses or concentrations:
Analytical determination demonstrated that dosing formulations contained the desired concentration of test item (85-101%).
Also stability at room temperature for the duration of the daily dosing period was shown.
Doses / concentrations
Remarks:
Doses / Concentrations:
0, 100, 500, 1000 mg/kg bw/day
Basis:
actual ingested
No. of animals per sex per dose:
12
Control animals:
yes, concurrent vehicle

Examinations

Fetal examinations:
live births, survival, body weight

Results and discussion

Results: maternal animals

Effect levels (maternal animals)

open allclose all
Dose descriptor:
NOAEL
Effect level:
> 1 000 mg/kg bw/day
Based on:
act. ingr.
Basis for effect level:
other: developmental toxicity
Dose descriptor:
NOAEL
Effect level:
> 1 000 mg/kg bw/day
Based on:
act. ingr.
Basis for effect level:
other: maternal toxicity

Results (fetuses)

Fetal abnormalities

Abnormalities:
not specified

Overall developmental toxicity

Developmental effects observed:
not specified

Any other information on results incl. tables

Concentration

(mg/kg bw/day)

0

100

500

1000

Mean % born alive

100

95.0

98.7

100

Total No of live fetuses

15.2

14.6

16.2

15.5

0-4 day viability

99.4

98.2

97.3

98.4

Mean fetal weight day 0

6.7

6.6

6.5

6.5

Mean fetal weight day 4

11.2

11.7

10.7

10.8

Sex ratio (male/female)

0.51

0.51

0.48

0.47

Applicant's summary and conclusion

Conclusions:
No adverse effects on maternal rats or pups were noted.
Executive summary:

A combined repeated dose toxicity Study with a Reproduction/Developmental Toxicity Screening Test was conducted following the OECD guideline 422, which was only published shortly after this study was performed.

Goups of each 12 male and female rats received 0, 100, 500 or 1000 mg/kg bw/day of Dodecanedioic acid by gavage. After 14 days of dosing rats were mated within the treatment groups and allowed to produce litters. Dosing continued through mating, gestation and laction until day 54.

On day 0 and 4 postpartum, pups in each litter were counted, weighed collectively by sex and exmined for abnormal behaviour or appearance.

Blood samples were collected from the male rats at the end of the study for hematological and clinical chemistry measurements.Parental animals were sacrificed for gross pathological examination. Selected organ weights were determined and control and high dose groups were subjected to histopathological examination.

Apart fom transient incidences of hyperactivity at high dose levels there were no clinicla signs. There were no mortalities, body weights, food consumption were not affected.

Reproductive performance was not affected by treatment. Pups showed no adverse effects of tratment.

No adverse effects were noted upon gross or histopathological examination or biochemistry of blood samples of parental rats.

A decrease in total leukocyte counts in samples of the high dose group had no morphological correlate in thymus or spleen.

Overall the NOAEL was observed at 1000 mg/kg bw/d the highest dose level, for both repeated dose toxicity and reproductive toxicity.